Peter T Scardino

Memorial Sloan-Kettering Cancer Center, New York, New York, United States

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Publications (741)4818.54 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Although life expectancy estimation is vital to decision making for localized prostate cancer, there are few, if any, valid and usable tools. Our goal was to create and validate a prediction model for other cause mortality in localized prostate cancer patients that could aid clinician’s initial treatment decisions at the point of care. Methods We combined an adjusted Social Security Administration table with a subset of comorbidities from a UK actuarial life expectancy model. Life tables were adjusted on the basis of survival data from a cohort of almost 10,000 radical prostatectomy patients treated at four major US academic institutions. Comorbidity-specific odds ratios were calculated and incorporated with baseline risk of mortality. We externally validated the model on 2898 patients from the Prostate Cancer Outcomes Study, which included men diagnosed with prostate cancer in six SEER cancer registries. These men had sufficient follow-up for our endpoints of 10- and 15-year mortality and also had self-reported comorbidity data. Results Life expectancy for prostate cancer patients were close to that of a typical US man who was 3 years younger. On external validation, 10- and 15-year concordance indexes were 0.724 and 0.726, respectively. Our model exhibited excellent calibration. Taking into account differences between how comorbidities are used in the model versus how they were recorded in the validation cohort, calibration would improve for most patients, but there would be overestimation of the risk of death in the oldest and sickest patients. Conclusions We successfully created and externally validated a new life expectancy prediction model that, while imperfect, has clear advantages to any alternative. We urge consideration of its use in counseling patients with localized prostate cancer.
    No preview · Article · Dec 2016 · BMC Medicine
  • Andrew J. Vickers · James A. Eastham · Peter T. Scardino · Hans Lilja
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    ABSTRACT: The Memorial Sloan-Kettering Cancer Center (MSKCC) recommendations on prostate cancer screening were developed in response to three limitations of previous screening guidelines: insufficient evidence-base, failure to link screening with treatment, and lack of risk stratification. The objective of the recommendations is to provide a schema for prostate cancer screening that maximizes the benefits, in terms of reduction in prostate cancer-specific mortality, and minimizes the harms, in terms of overdiagnosis and overtreatment. We recommend the following schema for men choosing to be screened following informed decision-making. Starting at age 45, PSA without DRE. If PSA ≥ 3 ng / mL: consider prostate biopsy; PSA ≥ 1 but < 3 ng / mL: return for PSA testing every 2 - 4 years; PSA < 1 ng / mL: return for PSA testing at 6 – 10 years. PSA testing should end at age 60 for men with PSA ≤ 1 ng/ mL; at 70, unless a man is very healthy and has a higher than average PSA; at 75 for all men. The decision to biopsy a man with a PSA > 3 ng / mL should be based on a variety of factors including repeat blood draw for confirmatory testing of the PSA level, DRE results, and work-up for benign disease. Additional reflex tests in blood such as a free-to-total PSA ratio, the Prostate Health Index, or 4Kscore, or urinary testing of PCA3, can also be informative in some patients. The best evidence suggests that more restricted indication for prostate biopsy and a more focused approach to pursue screening in men at highest risk of lethal cancer would retain most of the mortality benefits of aggressive screening schema, while importantly reducing harms from overdetection and overtreatment.
    No preview · Article · Feb 2016 · Urology
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    ABSTRACT: Purpose: We evaluated quality-of-life changes (QoL) in 907 patients treated with either radical prostatectomy (open or laparoscopic), real-time planned conformal brachytherapy, or high-dose intensity-modulated radiotherapy (IMRT) on a prospective IRB-approved longitudinal study. Methods: Validated questionnaires given pretreatment (baseline) and at 3, 6, 9, 12, 15, 18, 24, 36, and 48months addressed urinary function, urinary bother, bowel function, bowel bother, sexual function, and sexual bother. Results: At 48months, surgery had significantly higher urinary incontinence than others (both P<.001), but fewer urinary irritation/obstruction symptoms (all P<.001). Very low levels of bowel dysfunction were observed and only small subsets in each group showed rectal bleeding. Brachytherapy and IMRT showed better sexual function than surgery accounting for baseline function and other factors (delta 14.29 of 100, 95% CI, 8.57-20.01; and delta 10.5, 95% CI, 3.78-17.88). Sexual bother was similar. Four-year outcomes showed persistent urinary incontinence for surgery with more obstructive urinary symptoms for radiotherapy. Using modern radiotherapy delivery, bowel function deterioration is less-often observed. Sexual function was strongly affected in all groups yet significantly less for radiotherapy. Conclusions: Treatment selection should include patient preferences and balance predicted disease-free survival over a projected time vs potential impairment of QoL important for the patient.
    No preview · Article · Jan 2016 · Radiotherapy and Oncology
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    ABSTRACT: Background: We prospectively evaluated the safety and efficacy of adding preoperative chemoprophylaxis to our institution's operative venous thromboembolism (VTE) prophylaxis policy as part of a physician-led quality improvement initiative. Study design: Patients undergoing major cancer surgery between August 2013 and January 2014 were screened according to service-specific eligibility criteria and targeted to receive preoperative VTE chemoprophylaxis. Bleeding, transfusion, and VTE rates were compared with rates of historical controls who had not received preoperative chemoprophylaxis. Results: The 2,058 eligible patients who underwent operation between August 2013 and January 2014 (post-intervention) were compared with a cohort of 4,960 patients operated on between January 2012 and June 2013, who did not receive preoperative VTE chemoprophylaxis (pre-intervention). In total, 71% of patients in the post-intervention group were screened for eligibility; 82% received preoperative anticoagulation. When compared with the pre-intervention group, the post-intervention group had significantly lower transfusion rates (pre- vs post-intervention, 17% vs 14%; difference 3.5%, 95% CI 1.7% to 5%, p = 0.0003) without significant difference in major bleeding (difference 0.3%, 95% CI -0.1% to 0.7%, p = 0.2). Rates of deep venous thrombosis (1.3% vs 0.2%; difference 1.1%, 95% CI 0.7% to 1.4%, p < 0.0001) and pulmonary embolus (1.0% vs 0.4%; difference 0.6%, 95% CI 0.2% to 1%, p = 0.017) were significantly lower in the post-intervention group. Conclusions: In patients undergoing major cancer surgery, institution of a single dose of preoperative chemoprophylaxis, as part of a physician-led quality improvement initiative, did not increase bleeding or blood transfusions and was associated with a significant decrease in VTE rates.
    No preview · Article · Dec 2015 · Journal of the American College of Surgeons
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    ABSTRACT: Summary There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.
    Full-text · Article · Nov 2015 · Cell
  • Itay A Sternberg · Ian Vela · Peter T Scardino
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    ABSTRACT: A major dilemma in the selection of treatment for men with prostate cancer is the difficulty in accurately characterizing the risk posed by the cancer. This uncertainty has led physicians to recommend aggressive therapy for most men diagnosed with prostate cancer and has led to concerns about the benefits of screening and the adverse consequences of excessive treatment. Genomic analyses of prostate cancer reveal distinct patterns of alterations in the genomic landscape of the disease that show promise for improved prediction of prognosis and better medical decision making. Several molecular profiles are now commercially available and are being used to inform medical decisions. This article describes the clinical tests available for distinguishing aggressive from nonaggressive prostate cancer, reviews the new genomic tests, and discusses their advantages and limitations and the evidence for their utility in various clinical settings. Expected final online publication date for the Annual Review of Medicine Volume 67 is January 14, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
    No preview · Article · Oct 2015 · Annual review of medicine
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    ABSTRACT: Many men with elevated prostate-specific antigen (PSA) levels in serum do not have aggressive prostate cancer and undergo unnecessary biopsy. Retrospective studies using cryopreserved serum suggest that four kallikrein markers can predict biopsy outcome. Free, intact and total PSA, and kallikrein-related peptidase 2 were measured in cryopreserved blood from 6129 men with elevated PSA (≥3.0ng/mL) participating in the prospective, randomized trial Prostate Testing for Cancer and Treatment. Marker levels from 4765 men providing anticoagulated plasma were incorporated into statistical models to predict any-grade and high-grade (Gleason score ≥7) prostate cancer at 10-core biopsy. The models were corrected for optimism by 10-fold cross validation and independently validated using markers measured in serum from 1364 men. All statistical tests were two-sided. The four kallikreins enhanced prostate cancer detection compared with PSA and age alone. Area under the curve (AUC) for the four kallikreins was 0.719 (95% confidence interval [CI] = 0.704 to 0.734) vs 0.634 (95% CI = 0.617 to 0.651, P < .001) for PSA and age alone for any-grade cancer, and 0.820 (95% CI = 0.802 to 0.838) vs 0.738 (95% CI = 0.716 to 0.761) for high-grade cancer. Using a 6% risk of high-grade cancer as an illustrative cutoff, for 1000 biopsied men with PSA levels of 3.0ng/mL or higher, the model would reduce the need for biopsy in 428 men, detect 119 high-grade cancers, and delay diagnosis of 14 of 133 high-grade cancers. Models exhibited excellent discrimination on independent validation among men with only serum samples available for analysis. A statistical model based on kallikrein markers was validated in a large prospective study and reduces unnecessary biopsies while delaying diagnosis of high-grade cancers in few men. © The Author 2015. Published by Oxford University Press.
    No preview · Article · Jul 2015 · Journal of the National Cancer Institute
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    ABSTRACT: The natural history of prostate cancer is highly variable and difficult to predict accurately. Better markers are needed to guide management and avoid unnecessary treatment. In this study, we validate the prognostic value of a cell cycle progression score (CCP score) independently and in a prespecified linear combination with standard clinical variables, that is, a clinical-cell-cycle-risk (CCR) score. Paraffin sections from 761 men with clinically localized prostate cancer diagnosed by needle biopsy and managed conservatively in the United Kingdom, mostly between 2000 and 2003. The primary end point was prostate cancer death. Clinical variables consisted of centrally reviewed Gleason score, baseline PSA level, age, clinical stage, and extent of disease; these were combined into a single predefined risk assessment (CAPRA) score. Full data were available for 585 men who formed a fully independent validation cohort. In univariate analysis, the CCP score hazard ratio was 2.08 (95% CI (1.76, 2.46), P<10(-13)) for one unit change of the score. In multivariate analysis including CAPRA, the CCP score hazard ratio was 1.76 (95% CI (1.44, 2.14), P<10(-6)). The predefined CCR score was highly predictive, hazard ratio 2.17 (95% CI (1.83, 2.57), χ(2)=89.0, P<10(-20)) and captured virtually all available prognostic information. The CCP score provides significant pretreatment prognostic information that cannot be provided by clinical variables and is useful for determining which patients can be safely managed conservatively, avoiding radical treatment.British Journal of Cancer advance online publication, 23 June 2015; doi:10.1038/bjc.2015.223 www.bjcancer.com.
    Full-text · Article · Jun 2015 · British Journal of Cancer
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    ABSTRACT: The ability to visualize and spare nerves during surgery is critical for avoiding chronic morbidity, pain, and loss of function. Visualization of such critical anatomic structures is even more challenging during minimal access procedures because the small incisions limit visibility. In this study, we focus on improving imaging of nerves through the use of a new small molecule fluorophore, GE3126, used in conjunction with our dual-mode (color and fluorescence) laparoscopic imaging instrument. GE3126 has higher aqueous solubility, improved pharmacokinetics, and reduced non-specific adipose tissue fluorescence compared to previous myelin-binding fluorophores. Dosing and kinetics were initially optimized in mice. A non-clinical modified Irwin study in rats, performed to assess the potential of GE3126 to induce nervous system injuries, showed the absence of major adverse reactions. Real-time intraoperative imaging was performed in a porcine model. Compared to white light imaging, nerve visibility was enhanced under fluorescence guidance, especially for small diameter nerves obscured by fascia, blood vessels, or adipose tissue. In the porcine model, nerve visualization was observed rapidly, within 5 to 10 minutes post-intravenous injection and the nerve fluorescence signal was maintained for up to 80 minutes. The use of GE3126, coupled with practical implementation of an imaging instrument may be an important step forward in preventing nerve damage in the operating room.
    Full-text · Article · Jun 2015 · PLoS ONE
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    ABSTRACT: Genome-wide association studies have identified multiple single-nucleotide polymorphsims (SNPs) associated with prostate cancer (PCa). Although these SNPs have been clearly associated with disease risk, their relationship with clinical outcomes is less clear. Our aim was to assess the frequency of known PCa susceptibility alleles within a single institution ascertainment and to correlate risk alleles with disease-specific outcomes. We genotyped 1354 individuals treated for localised PCa between June 1988 and December 2007. Blood samples were prospectively collected and de-identified before being genotyped and matched to phenotypic data. We investigated associations between 61 SNPs and disease-specific end points using multivariable analysis and also determined if SNPs were associated with PSA at diagnosis. Seven SNPs showed associations on multivariable analysis (P<0.05), rs13385191 with both biochemical recurrence (BR) and castrate metastasis (CM), rs339331 (BR), rs1894292, rs17178655 and rs11067228 (CM), and rs11902236 and rs4857841 PCa-specific mortality. After applying a Bonferroni correction for number of SNPs (P<0.0008), the only persistent significant association was between rs17632542 (KLK3) and PSA levels at diagnosis (P=1.4 × 10(-5)). We confirmed that rs17632542 in KLK3 is associated with PSA at diagnosis. No significant association was seen between loci and disease-specific end points when accounting for multiple testing. This provides further evidence that known PCa risk SNPs do not predict likelihood of disease progression.British Journal of Cancer advance online publication 11 June 2015; doi:10.1038/bjc.2015.199 www.bjcancer.com.
    No preview · Article · Jun 2015 · British Journal of Cancer

  • No preview · Article · Apr 2015 · European Urology Supplements
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    Preview · Article · Apr 2015 · The Journal of Urology
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    Full-text · Article · Apr 2015 · The Journal of Urology
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    ABSTRACT: To evaluate whether the number of preoperative prostate biopsies affects functional outcomes after radical prostatectomy (RP). We identified men treated with RP at our institution between 2008 and 2011. At 6 and 12 months post-operatively, patients completed questionnaires assessing erectile and urinary function. Men with preoperative incontinence or erectile dysfunction or who did not complete the questionnaire were excluded. Primary outcomes were urinary and erectile function at 12 months postoperatively. We used logistic regression to estimate the impact of number of prostate biopsies on functional outcomes after adjusting for demographic and clinical factors. We identified 2,712 men treated with RP between 2008 and 2011. Most men (80%) had 1 preoperative prostate biopsy, 16% had 2, and 4% had at least 3. On adjusted analysis, erectile function at 12 months was not significantly different for men with 2 (OR 1.25; 95% CI 0.90, 1.75) or 3 or more (OR 1.52; 95% CI 0.84, 2.78) biopsies, compared to those with 1. Similarly, urinary function at 12 months was not significantly different for men with 2 (0.84, 95% CI 0.64, 1.10) or 3 or more (0.99, 95% CI 0.60, 1.61) biopsies compared to those with 1. We did not find evidence that more preoperative prostate biopsies adversely affected erectile or urinary function at 12 months following RP. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Apr 2015 · The Journal of Urology
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    Preview · Article · Apr 2015 · The Journal of Urology
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    Preview · Article · Apr 2015 · The Journal of Urology
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    Full-text · Article · Apr 2015 · The Journal of Urology
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    ABSTRACT: Previous studies of prostate cancer (PCa) risk and anthropometrics (ie, body measurements) were based on single measurements or obtained over limited time spans. To study the association between anthropometrics measured at multiple time points in life and their relation to later diagnosis, metastasis, or death from PCa. This case-control study includes 27 167 Swedish men enrolled in two population-based projects from 1974 to 1996. PCa diagnosis up to December 31, 2006, disease information, gestation time, and anthropometrics at birth, military conscript testing, and adulthood were collected. A total of 1355 PCa cases were matched with 5271 controls. Univariate conditional logistic regression was used to determine whether clinical diagnosis, metastasis, or PCa death was associated with low birth weight (weight <2500g); with small size for gestational age; or with weight, length, or body mass index (BMI) at birth, adolescence (aged 16-22 yr), or early middle age (aged 44-50 yr). Apart from weight at adolescence, which was associated with an increased risk of PCa diagnosis (odds ratio [OR] per 5kg: 1.05; 95% confidence interval [CI], 1.01-1.09; p=0.026), preadulthood measurements were not associated with any PCa end point. Adulthood parameters were not associated with diagnosis. In contrast, weight and BMI at early middle age were significantly associated with metastasis (OR per 5kg: 1.13; 95% CI, 1.06-1.20; p<0.0001, and OR: 1.09; 95% CI, 1.05-1.14; p<0.0001) and death (OR per 5kg: 1.11 (95% CI, 1.03-1.19; p=0.005, and OR: 1.08; 95% CI, 1.03-1.13; p=0.003), respectively. It remains unclear whether these results apply to men of nonwhite origin, to populations with active PCa screening programs, or to countries without socialized health care. The analyses of these large data sets demonstrate that significant effects of body characteristics (with links to metabolic syndrome) measured at early middle age are associated with PCa disease severity, metastatic progression, and outcome. Conversely, measurements at birth and adolescence are not associated with PCa prevalence or outcome. Increased weight and body mass index in adults is associated with a higher risk of prostate cancer metastasis and death. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    No preview · Article · Mar 2015 · European Urology

  • No preview · Conference Paper · Mar 2015
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    ABSTRACT: Introduction: We evaluated the safety and efficacy of a clinical pathway designed and implemented to transition inpatient minimally invasive radical prostatectomy to a procedure with overnight observation. Methods: In April 2011 ambulatory extended recovery was implemented at our institution. This was a multidisciplinary program of preoperative teaching and postoperative care for patients undergoing minimally invasive radical prostatectomy. We compared the risk of requiring a more than 1-night hospital stay by patients treated with surgery the year before the program vs those treated after the program was initiated, adjusting for age, ASA® status and surgery type. We also examined the rates of readmission and urgent care visits within 48 hours, and 7 and 30 days before and after the program began. Results: The proportion of patients who stayed longer than 1 night was 53% in the year before initiating the ambulatory extended recovery program vs 8% during the program, representing an adjusted absolute risk decrease of 45% (95% CI 39-50, p <0.0001). There was no important predictor of a greater than 1-night length of stay among ambulatory extended recovery patients. Rates of readmission and urgent care visits were slightly lower during the ambulatory extended recovery phase with no significant difference between the groups. Conclusions: The ambulatory extended recovery program successfully transitioned most patients to a 1-night hospital stay without resulting in an increased rate of readmission or urgent care visits. © 2015 American Urological Association Education and Research, Inc.
    No preview · Article · Feb 2015 · Urology Practice

Publication Stats

42k Citations
4,818.54 Total Impact Points

Institutions

  • 1999-2016
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Surgery
      • • Epidemiology & Biostatistics Group
      • • Department of Pathology
      New York, New York, United States
    • Texas A&M University - Galveston
      Galveston, Texas, United States
  • 2015
    • Queen Mary, University of London
      Londinium, England, United Kingdom
  • 2012-2014
    • Cornell University
      Итак, New York, United States
  • 2010-2012
    • Gracie Square Hospital, New York, NY
      New York, New York, United States
    • University of Ottawa
      • Department of Surgery
      Ottawa, Ontario, Canada
  • 2011
    • CUNY Graduate Center
      New York, New York, United States
  • 2007-2010
    • University of Turku
      Turku, Varsinais-Suomi, Finland
  • 2008-2009
    • Columbia University
      New York, New York, United States
    • Weill Cornell Medical College
      • Department of Urology
      New York City, New York, United States
  • 2002-2008
    • University of Hamburg
      Hamburg, Hamburg, Germany
    • Medical University of South Carolina
      • Department of Urology
      Charleston, SC, United States
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
    • University Medical Center Hamburg - Eppendorf
      • Department of Urology
      Hamburg, Hamburg, Germany
  • 2005
    • State University of New York Downstate Medical Center
      • Department of Urology
      Brooklyn, NY, United States
  • 1983-2004
    • Baylor College of Medicine
      • Department of Urology
      Houston, Texas, United States
  • 1991-1999
    • Houston Methodist Hospital
      Houston, Texas, United States
  • 1997
    • Case Western Reserve University
      Cleveland, Ohio, United States
  • 1995
    • University of Southern California
      • Department of Urology
      Los Angeles, California, United States
    • Prostate Cancer Research Institute
      Los Angeles, California, United States
  • 1994
    • Houston medical Center
      Ворнер Робинс, Georgia, United States
    • Loyola University Medical Center
      • Department of Urology
      مايوود، إلينوي, Illinois, United States
  • 1993
    • National Cancer Institute (USA)
      Maryland, United States